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Article(id=1203061224012488719, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203061212524290053, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2023.01.0078, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1643212800000, receivedDateStr=2022-01-27, revisedDate=null, revisedDateStr=null, acceptedDate=1649520000000, acceptedDateStr=2022-04-10, onlineDate=1764761747600, onlineDateStr=2025-12-03, pubDate=1674835200000, pubDateStr=2023-01-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1764761747600, onlineIssueDateStr=2025-12-03, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1764761747600, creator=13701087609, updateTime=1764761747600, updator=13701087609, issue=Issue{id=1203061212524290053, tenantId=1146029695717560320, journalId=1189873630562394117, year='2023', volume='48', issue='1', pageStart='1', pageEnd='120', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1764761744816, creator=13701087609, updateTime=1764763211166, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1203067362732913657, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203061212524290053, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1203067362732913658, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203061212524290053, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=78, endPage=83, ext={EN=ArticleExt(id=1203061226126417951, articleId=1203061224012488719, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Analysis of risk factors for thrombotic events in trauma patients based on random forest algorithm, columnId=1190310109000602400, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Clinical Research, runingTitle=null, highlight=null, articleAbstract=

Objective To explore the risk factors of thrombotic events in trauma patients by using random forest algorithm. Methods The data of 255 trauma patients admitted to the intensive care unit from July 2016 to December 2021 were retrospectively analyzed. These patients were divided into thrombosis group and non-thrombosis group by propensity score matching and according to the occurrence of thrombosis after trauma. The risk factors of 24 clinical variables including age, gender, injury severity score (ISS), acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), white blood cell count, red blood cell count, platelet count, hemoglobin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, creatinine, total protein, prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, fibrin degradation products, D-dimer, antithrombin 3, coagulation reaction time (CRT), clot formation rate, clot formation kinetics and maximum clot strength (maximal amplitude, MA) within 2 hours after admission were analyzed by random forest algorithm. The predictive values of the variables were evaluated by receiver operating characteristic (ROC) curve and verified by bootstrap method. Results One hundred and ten trauma patients were divided into thrombosis group (n=22) and non-thrombosis group (n=88) by propensity score matching. The results of random forest algorithms showed that high MA level was an important risk factor for thrombotic events after trauma(P<0.05). The area under ROC curve (AUC) of using MA value to predict thrombotic events in trauma patients was 0.70 (95%CI 0.56-0.81, P<0.01), and the bootstrap method confirmed that the AUC of using MA value to predict thrombotic events in trauma patients was 0.70 (95%CI 0.57-0.80, P<0.01). When the cut-off value of MA was 63.3 mm, the sensitivity and specificity of the trauma patients suffering thrombotic events were 63.6% and 78.4%, respectively. Conclusion The high MA level is an important risk factor for thrombotic events in trauma patients.

, correspAuthors=Jing-Chun Song, authorNote=null, correspAuthorsNote=
E-mail:
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目的 采用随机森林算法探讨创伤患者并发血栓事件的危险因素。方法 回顾性分析解放军联勤保障部队第908医院重症医学科2016年7月—2021年12月收治的255例创伤患者的临床资料，通过倾向性评分匹配纳入，并按创伤后是否新发血栓事件分为血栓组与无血栓组。应用随机森林算法对基础指标年龄、性别，入科时创伤严重程度(ISS)评分、急性生理与慢性健康(APACHE)Ⅱ评分，入科后2 h的白细胞计数、红细胞计数、血小板计数及血红蛋白水平，生化指标谷丙转氨酶、谷草转氨酶、总胆红素、肌酐及总蛋白，凝血常规指标凝血酶原时间、活化部分凝血活酶时间、凝血酶时间、纤维蛋白原、纤维蛋白原降解产物、D-二聚体、抗凝血酶3，血栓弹力图指标凝血反应时间、血块形成速率、血块形成动力学、血块最大强度(MA)等24个临床变量进行危险因素分析；采用受试者工作特征(ROC)曲线评价变量的预测价值，并应用bootstrap法进行验证。结果 经倾向性评分匹配后共纳入创伤患者110例，其中血栓组22例，无血栓组88例；随机森林算法结果显示，血栓弹力图的MA值高是创伤后血栓事件的危险因素(P<0.05)。应用MA值预测创伤患者发生血栓事件的ROC曲线下面积(AUC)为0.70(95%CI 0.56~0.81，P<0.01)，采用bootstrap法验证得出AUC为0.70(95%CI 0.57~0.80，P<0.01)。当MA的界值为63.3 mm时，预测创伤患者发生血栓事件的敏感度为63.6%，特异度为78.4%。结论 血栓弹力图的MA值高是创伤患者并发血栓事件的重要危险因素。

, correspAuthors=宋景春, authorNote=null, correspAuthorsNote=
宋景春，E-mail：
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张昕，医学学士，主治医师，主要从事弥散性血管内凝血中西医结合治疗方面的研究

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张昕，医学学士，主治医师，主要从事弥散性血管内凝血中西医结合治疗方面的研究

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张昕，医学学士，主治医师，主要从事弥散性血管内凝血中西医结合治疗方面的研究

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Acad Emerg Med, 2020, 27(5): 358-365., articleTitle=Mortality and complication rates in adult trauma patients receiving tranexamic acid: a single-center experience in the post-CRASH-2 era, refAbstract=null), Reference(id=1203061240764539391, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203061224012488719, doi=null, pmid=null, pmcid=null, year=2021, volume=47, issue=12, pageStart=1368, pageEnd=1392, url=null, language=null, rfNumber=[20], rfOrder=21, authorNames=Vlaar APJ, Dionne JC, de Bruin S, journalName=Intensive Care Med, refType=null, unstructuredReference=Vlaar APJ, Dionne JC, de Bruin S, et al. Transfusion strategies in bleeding critically ill adults: a clinical practice guideline from the European Society of Intensive Care Medicine[J]. 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%IncMSE. 均方误差增长百分比；*P<0.05

, figureFileSmall=zqFF4U7UkFOBZRCT9xwq6A==, figureFileBig=o8QbFlVFa8RWPj448g0WPw==, tableContent=null), ArticleFig(id=1203061235769123162, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203061224012488719, language=EN, label=Fig. 2, caption=ROC curve of MA value predicting thrombotic events in trauma patients, figureFileSmall=BcvWa3iOnZuFfO2tnC9z3Q==, figureFileBig=Aa/HLt/ipt77KnBCay+Xzw==, tableContent=null), ArticleFig(id=1203061235911729505, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203061224012488719, language=CN, label=图2, caption=MA预测创伤患者发生血栓事件的ROC曲线

AUC. 曲线下面积

, figureFileSmall=BcvWa3iOnZuFfO2tnC9z3Q==, figureFileBig=Aa/HLt/ipt77KnBCay+Xzw==, tableContent=null), ArticleFig(id=1203061236058530152, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203061224012488719, language=EN, label=Tab. 1, caption=

Comparison of basic data between the two groups of trauma patients before and after propensity score matching

, figureFileSmall=null, figureFileBig=null, tableContent=
项目PSM前PSM后
无血栓组(n=233)血栓组(n=22)t/χ2/UP无血栓组(n=88)血栓组(n=22)t/χ2/UP
年龄(岁，$\bar{x}±s$)50±1864±193.3530.00160±1864±190.9770.331
男/女(例)174/5914/81.2650.26162/2614/80.3830.536
白细胞计数[×109/L,M(Q1,Q3)]11.9(8.8,15.2)10.5(8.3,13.5)1.2260.22010.8(7.8,13.6)10.5(8.3,13.5)0.0640.949
红细胞计数(×1012/L, $\bar{x}±s$)3.2±0.83.1±0.90.5840.5603.1±0.73.1±0.90.2550.799
血红蛋白(g/L, $\bar{x}±s$)97±2693±240.7720.44192±2193±240.1800.858
血小板计数[×109/L,M(Q1,Q3)]115(84,178)147(112,212)1.6440.100106(82,173)147(112,212)1.8500.064
谷丙转氨酶[U/L,M(Q1,Q3)]37.9(21.0,68.5)29.1(12.8,56.6)1.3910.16427.3(17.8,55.0)29.1(12.8,56.6)0.2390.811
谷草转氨酶[U/L,M(Q1,Q3)]52.3(29.3,116.3)35.7(22.5,124.5)1.1700.24239.4(26.3,77.7)35.7(22.5,124.5)0.2470.805
总胆红素[μmol/L,M(Q1,Q3)]13.6(9.5,21.2)15.9(11.9,26.2)1.5230.12814.2(9.9,23.0)15.9(11.9,26.2)1.0540.292
总蛋白(g/L, $\bar{x}±s$)50±1255±91.7170.08753±1155±90.8180.415
肌酐[μmol/L,M(Q1,Q3)]71.4(55.6,97.2)72.2(53.8,97.4)0.1090.91367.5(50.3,96.9)72.2(53.8,97.4)0.6950.487
ISS评分[[分，M(Q1,Q3)]22(17,29)18(10,26)1.9100.05622(15,25)18(10,26)0.9230.356
APACHEⅡ评分(分，$\bar{x}±s$)18.68±6.2420.00±4.850.9620.33720.20±5.7120.00±4.850.1550.877
ICU住院时间[d,M(Q1,Q3)]13(6,23)9(6,30)0.0820.93510(4,20)9(6,30)0.8300.406
ICU病死率[n(%)]19(8.15)3(13.64)0.7660.3818(9.09)3(13.64)0.0570.812
PT[s,M(Q1,Q3)]14.7(12.7,17.4)12.8(12.3,16.0)1.6150.10614.2(12.5,16.3)12.8(12.3,16.0)0.5720.567
APTT[s,M(Q1,Q3)]33.1(27.5,43.3)29.6(25.7,35.1)2.1110.03530.9(27.2,40.1)29.6(25.7,35.1)1.2670.205
TT[s,M(Q1,Q3)]14.6(11.7,17.2)14.3(14.0,16.4)0.4760.63414.8(12.4,17.0)14.3(14.0,16.4)0.1910.849
FIB[g/L,M(Q1,Q3)]2.02(1.35,3.18)3.25(2.41,4.00)3.0450.0022.17(1.58,3.39)3.25(2.41,4.00)2.4510.014
FDP[μg/ml,M(Q1,Q3)]29.74(11.60,61.36)15.93(8.08,22.52)2.7530.00629.22(10.74,58.76)15.93(8.08,22.52)2.3840.017
D-二聚体[μg/ml,M(Q1,Q3)]7.78(3.39,21.21)4.59(2.95,7.51)2.3810.0177.04(3.53,21.88)4.59(2.95,7.51)2.2120.027
AT3[%,M(Q1,Q3)]69(55,82)82(73,102)2.5820.01073(56,82)82(73,102)2.0600.039
R[min,M(Q1,Q3)]6.7(5.3,8.4)7.4(5.5,8.8)0.3890.6986.5(5.1,8.2)7.4(5.5,8.8)0.6910.489
K[min,M(Q1,Q3)]2.5(1.9,4.2)1.8(1.3,2.5)3.0540.0022.4(1.8,4.2)1.8(1.3,2.5)2.3970.017
Angle[°,M(Q1,Q3)]56.0(43.4,63.8)64.5(54.6,70.9)3.0530.00258.8(46.6,65.1)64.5(54.6,70.9)2.3350.020
MA(mm, $\bar{x}±s$)51.7±13.861.4±12.03.1830.00253.1±14.461.4±12.02.4730.015
LY30[%,M(Q1,Q3)]0.1(0.0,0.5)0.0(0.0,0.5)1.0150.3100.1(0.0,0.7)0.0(0.0,0.5)1.4230.155
CI[M(Q1,Q3)]–2.0(–5.3,0.0)–0.9(–2.6,1.2)2.1060.035–1.7(–5.0,0.0)–0.9(–2.6,1.2)1.5860.113
), ArticleFig(id=1203061236209525102, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203061224012488719, language=CN, label=表1, caption=

倾向性评分匹配前后两组创伤患者基线资料比较

, figureFileSmall=null, figureFileBig=null, tableContent=
项目PSM前PSM后
无血栓组(n=233)血栓组(n=22)t/χ2/UP无血栓组(n=88)血栓组(n=22)t/χ2/UP
年龄(岁，$\bar{x}±s$)50±1864±193.3530.00160±1864±190.9770.331
男/女(例)174/5914/81.2650.26162/2614/80.3830.536
白细胞计数[×109/L,M(Q1,Q3)]11.9(8.8,15.2)10.5(8.3,13.5)1.2260.22010.8(7.8,13.6)10.5(8.3,13.5)0.0640.949
红细胞计数(×1012/L, $\bar{x}±s$)3.2±0.83.1±0.90.5840.5603.1±0.73.1±0.90.2550.799
血红蛋白(g/L, $\bar{x}±s$)97±2693±240.7720.44192±2193±240.1800.858
血小板计数[×109/L,M(Q1,Q3)]115(84,178)147(112,212)1.6440.100106(82,173)147(112,212)1.8500.064
谷丙转氨酶[U/L,M(Q1,Q3)]37.9(21.0,68.5)29.1(12.8,56.6)1.3910.16427.3(17.8,55.0)29.1(12.8,56.6)0.2390.811
谷草转氨酶[U/L,M(Q1,Q3)]52.3(29.3,116.3)35.7(22.5,124.5)1.1700.24239.4(26.3,77.7)35.7(22.5,124.5)0.2470.805
总胆红素[μmol/L,M(Q1,Q3)]13.6(9.5,21.2)15.9(11.9,26.2)1.5230.12814.2(9.9,23.0)15.9(11.9,26.2)1.0540.292
总蛋白(g/L, $\bar{x}±s$)50±1255±91.7170.08753±1155±90.8180.415
肌酐[μmol/L,M(Q1,Q3)]71.4(55.6,97.2)72.2(53.8,97.4)0.1090.91367.5(50.3,96.9)72.2(53.8,97.4)0.6950.487
ISS评分[[分，M(Q1,Q3)]22(17,29)18(10,26)1.9100.05622(15,25)18(10,26)0.9230.356
APACHEⅡ评分(分，$\bar{x}±s$)18.68±6.2420.00±4.850.9620.33720.20±5.7120.00±4.850.1550.877
ICU住院时间[d,M(Q1,Q3)]13(6,23)9(6,30)0.0820.93510(4,20)9(6,30)0.8300.406
ICU病死率[n(%)]19(8.15)3(13.64)0.7660.3818(9.09)3(13.64)0.0570.812
PT[s,M(Q1,Q3)]14.7(12.7,17.4)12.8(12.3,16.0)1.6150.10614.2(12.5,16.3)12.8(12.3,16.0)0.5720.567
APTT[s,M(Q1,Q3)]33.1(27.5,43.3)29.6(25.7,35.1)2.1110.03530.9(27.2,40.1)29.6(25.7,35.1)1.2670.205
TT[s,M(Q1,Q3)]14.6(11.7,17.2)14.3(14.0,16.4)0.4760.63414.8(12.4,17.0)14.3(14.0,16.4)0.1910.849
FIB[g/L,M(Q1,Q3)]2.02(1.35,3.18)3.25(2.41,4.00)3.0450.0022.17(1.58,3.39)3.25(2.41,4.00)2.4510.014
FDP[μg/ml,M(Q1,Q3)]29.74(11.60,61.36)15.93(8.08,22.52)2.7530.00629.22(10.74,58.76)15.93(8.08,22.52)2.3840.017
D-二聚体[μg/ml,M(Q1,Q3)]7.78(3.39,21.21)4.59(2.95,7.51)2.3810.0177.04(3.53,21.88)4.59(2.95,7.51)2.2120.027
AT3[%,M(Q1,Q3)]69(55,82)82(73,102)2.5820.01073(56,82)82(73,102)2.0600.039
R[min,M(Q1,Q3)]6.7(5.3,8.4)7.4(5.5,8.8)0.3890.6986.5(5.1,8.2)7.4(5.5,8.8)0.6910.489
K[min,M(Q1,Q3)]2.5(1.9,4.2)1.8(1.3,2.5)3.0540.0022.4(1.8,4.2)1.8(1.3,2.5)2.3970.017
Angle[°,M(Q1,Q3)]56.0(43.4,63.8)64.5(54.6,70.9)3.0530.00258.8(46.6,65.1)64.5(54.6,70.9)2.3350.020
MA(mm, $\bar{x}±s$)51.7±13.861.4±12.03.1830.00253.1±14.461.4±12.02.4730.015
LY30[%,M(Q1,Q3)]0.1(0.0,0.5)0.0(0.0,0.5)1.0150.3100.1(0.0,0.7)0.0(0.0,0.5)1.4230.155
CI[M(Q1,Q3)]–2.0(–5.3,0.0)–0.9(–2.6,1.2)2.1060.035–1.7(–5.0,0.0)–0.9(–2.6,1.2)1.5860.113
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基于随机森林算法的创伤患者并发血栓事件危险因素分析
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张昕 , 钟林翠 , 吴峻 , 胡艳晶 , 宋晓敏 , 宋景春 *
解放军医学杂志 | 临床研究 2023,48(1): 78-83
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解放军医学杂志 | 临床研究 2023, 48(1): 78-83
基于随机森林算法的创伤患者并发血栓事件危险因素分析
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张昕, 钟林翠, 吴峻, 胡艳晶, 宋晓敏, 宋景春*
作者信息
  • 解放军联勤保障部队第908医院重症医学科/南昌市血栓与止血学重点实验室，江西南昌 330002

    • 张昕，医学学士，主治医师，主要从事弥散性血管内凝血中西医结合治疗方面的研究

通讯作者:

宋景春，E-mail：
Analysis of risk factors for thrombotic events in trauma patients based on random forest algorithm
Xin Zhang, Lin-Cui Zhong, Jun Wu, Yan-Jing Hu, Xiao-Min Song, Jing-Chun Song*
Affiliations
  • Intensive Care Unit, the 908th Hospital of Chinese PLA Logistical Support Force/Nanchang Key Laboratory of Thrombosis and Hemostasis, Nanchang, Jiangxi 330002, China
出版时间: 2023-01-28 doi: 10.11855/j.issn.0577-7402.2023.01.0078
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摘要
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目的 采用随机森林算法探讨创伤患者并发血栓事件的危险因素。方法 回顾性分析解放军联勤保障部队第908医院重症医学科2016年7月—2021年12月收治的255例创伤患者的临床资料，通过倾向性评分匹配纳入，并按创伤后是否新发血栓事件分为血栓组与无血栓组。应用随机森林算法对基础指标年龄、性别，入科时创伤严重程度(ISS)评分、急性生理与慢性健康(APACHE)Ⅱ评分，入科后2 h的白细胞计数、红细胞计数、血小板计数及血红蛋白水平，生化指标谷丙转氨酶、谷草转氨酶、总胆红素、肌酐及总蛋白，凝血常规指标凝血酶原时间、活化部分凝血活酶时间、凝血酶时间、纤维蛋白原、纤维蛋白原降解产物、D-二聚体、抗凝血酶3，血栓弹力图指标凝血反应时间、血块形成速率、血块形成动力学、血块最大强度(MA)等24个临床变量进行危险因素分析；采用受试者工作特征(ROC)曲线评价变量的预测价值，并应用bootstrap法进行验证。结果 经倾向性评分匹配后共纳入创伤患者110例，其中血栓组22例，无血栓组88例；随机森林算法结果显示，血栓弹力图的MA值高是创伤后血栓事件的危险因素(P<0.05)。应用MA值预测创伤患者发生血栓事件的ROC曲线下面积(AUC)为0.70(95%CI 0.56~0.81，P<0.01)，采用bootstrap法验证得出AUC为0.70(95%CI 0.57~0.80，P<0.01)。当MA的界值为63.3 mm时，预测创伤患者发生血栓事件的敏感度为63.6%，特异度为78.4%。结论 血栓弹力图的MA值高是创伤患者并发血栓事件的重要危险因素。

创伤和损伤  /  血栓形成  /  随机森林算法  /  血块最大强度

Objective To explore the risk factors of thrombotic events in trauma patients by using random forest algorithm. Methods The data of 255 trauma patients admitted to the intensive care unit from July 2016 to December 2021 were retrospectively analyzed. These patients were divided into thrombosis group and non-thrombosis group by propensity score matching and according to the occurrence of thrombosis after trauma. The risk factors of 24 clinical variables including age, gender, injury severity score (ISS), acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), white blood cell count, red blood cell count, platelet count, hemoglobin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, creatinine, total protein, prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, fibrin degradation products, D-dimer, antithrombin 3, coagulation reaction time (CRT), clot formation rate, clot formation kinetics and maximum clot strength (maximal amplitude, MA) within 2 hours after admission were analyzed by random forest algorithm. The predictive values of the variables were evaluated by receiver operating characteristic (ROC) curve and verified by bootstrap method. Results One hundred and ten trauma patients were divided into thrombosis group (n=22) and non-thrombosis group (n=88) by propensity score matching. The results of random forest algorithms showed that high MA level was an important risk factor for thrombotic events after trauma(P<0.05). The area under ROC curve (AUC) of using MA value to predict thrombotic events in trauma patients was 0.70 (95%CI 0.56-0.81, P<0.01), and the bootstrap method confirmed that the AUC of using MA value to predict thrombotic events in trauma patients was 0.70 (95%CI 0.57-0.80, P<0.01). When the cut-off value of MA was 63.3 mm, the sensitivity and specificity of the trauma patients suffering thrombotic events were 63.6% and 78.4%, respectively. Conclusion The high MA level is an important risk factor for thrombotic events in trauma patients.

wounds and injuries  /  thrombosis  /  random forest algorithm  /  maximum clot strength (maximum amplitude)
张昕, 钟林翠, 吴峻, 胡艳晶, 宋晓敏, 宋景春. 基于随机森林算法的创伤患者并发血栓事件危险因素分析. 解放军医学杂志, 2023 , 48 (1) : 78 -83 . DOI: 10.11855/j.issn.0577-7402.2023.01.0078
Xin Zhang, Lin-Cui Zhong, Jun Wu, Yan-Jing Hu, Xiao-Min Song, Jing-Chun Song. Analysis of risk factors for thrombotic events in trauma patients based on random forest algorithm[J]. Medical Journal of Chinese People’s Liberation Army, 2023 , 48 (1) : 78 -83 . DOI: 10.11855/j.issn.0577-7402.2023.01.0078
正文
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创伤是全球40岁以下人群死亡的首要因素，所致死亡人数在疾病死亡谱中居第3位[1-2]。既往研究认为，创伤后大出血是导致死亡的主要原因[3-4]。近年研究发现，创伤后患者高凝状态的发生率为26%[5]，血栓栓塞事件的发生率为10%~30%[6-8]。创伤后出现脑梗死、心肌梗死、深静脉血栓形成及肺栓塞等血栓事件是创伤患者1年内死亡的主要原因[9]。因此，筛选出创伤后可能发生血栓的高危患者并进行积极预防、治疗尤为重要。有研究针对创伤患者发生深静脉血栓的危险因素进行分析发现，深静脉血栓形成与损伤严重程度、损伤部位、伴随疾病、手术次数等因素相关[10-11]。创伤后血栓形成的病理生理机制不仅包括组织损伤，更与凝血功能异常有关[12]。本研究对有完整凝血功能指标的创伤患者进行回顾性分析，筛选创伤后发生血栓事件的危险因素。
1 资料与方法
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1.1 研究对象
解放军联勤保障部队第908医院重症医学科2016年7月-2021年12月收治的创伤患者255例，其中男188例，女67例，年龄(51.6±18.2)岁。纳入标准：(1)年龄≥16岁；(2)ICU住院时间>24 h。排除标准：(1)入科时已经发现血栓事件；(2)过去12个月内有血栓事件或出血性疾病史；(3)存在已知的先天性凝血功能紊乱；(4)存在中重度肝病；(5)近1个月内接受过抗凝药物、糖皮质激素或免疫抑制剂治疗；(6)正在接受抗凝治疗的患者。上述创伤患者按创伤后是否新发血栓事件分为血栓组(n=22)与无血栓组(n=233)。血栓组创伤后发生血栓栓塞事件的中位时间[M(Q1，Q3)]为6(2，15) d，其中下肢静脉血栓8例，脑梗死7例，肺栓塞6例，下肢动脉血栓1例。以患者的性别、年龄进行倾向性评分匹配(propensity score matching，PSM)。本研究获解放军联勤保障部队第908医院伦理委员会批准(908yyLL028)。
1.2 评价指标
通过住院电子病历系统采集创伤患者的临床资料，主要包括年龄、性别，入科时的创伤严重程度(injury severity score，ISS)评分、急性生理与慢性健康(acute physiology and chronic health evaluation，APACHE)Ⅱ评分，ICU住院时间及病死情况。收集实验室指标，包括入科后2 h的白细胞、红细胞、血小板计数及血红蛋白(深圳迈瑞BC-6900全自动血常规分析仪)；谷丙转氨酶、谷草转氨酶、总胆红素、肌酐及总蛋白(深圳迈瑞BS-2000全自动生化分析仪)；凝血酶原时间(prothrombin time，PT)、活化部分凝血活酶时间(activated partial thromboplastin time，APTT)、凝血酶时间(thrombin time，TT)、纤维蛋白原(fibrinogen，FIB)、纤维蛋白原降解产物(fibrin degradation products，FDP)、D-二聚体及抗凝血酶(antithrombin，AT)3(美国沃芬ACL-TOP700全自动血凝分析仪)；凝血反应时间(reaction time，R)、血块形成速率(kinetics of clot development，K)、血块形成动力学(Angle)、血块最大强度(maximum amplitude，MA)、30 min凝块溶解分数(lysis at 30 min，LY30)及凝血综合指数(coagulation index，CI)(北京乐普CFMS LEPU-8800血栓弹力图仪)。
1.3 研究方法
比较两组创伤患者PSM前后基线资料；采用随机森林算法对上述变量进行分析，以创伤后是否发生血栓事件为响应变量，评估预测变量的相对重要性并筛选重要的预测变量；筛选变量后进行受试者工作特征(receiver operating characteristic，ROC)曲线分析，并采用bootstrap法(Stata15中bootstrap命令设置200次迭代)进行验证。根据获得的临界值将创伤患者再次分组，比较组间血栓事件发生率的差异。
1.4 统计学处理
数据采用SPSS 26.0、Stata 15及R 4.1.2统计软件进行分析。计数资料以例表示，采用χ2检验。计量资料采用单样本S-W法进行正态分布检验，符合正态分布的数据以$\bar{x}±s$表示，非正态分布的数据以M(Q1，Q3)表示。满足正态分布且方差齐者数据比较采用t检验，不满足者采用非参数Mann-Whitney U检验。使用R包“Match It”进行PSM，采用“邻近法”，比例为1:4，卡钳值0.1进行匹配。使用R包“randomForest”“rfPermute”及“ggplot2”进行随机森林分析。P<0.05为差异有统计学意义。
2 结果
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2.1 两组创伤患者基线资料比较
PSM前，血栓组与无血栓组创伤患者年龄差异有统计学意义(P<0.05)；经PSM均衡组间基线资料，匹配后血栓组纳入22例，无血栓组纳入88例，其中男76例，女34例，年龄(60.4±18.2)岁，两组年龄差异无统计学意义(P>0.05)。PSM前，两组性别、白细胞计数、红细胞计数、血红蛋白、血小板计数、谷丙转氨酶、谷草转氨酶、总胆红素、总蛋白、肌酐、ISS评分、APACHEⅡ评分、ICU住院时间及ICU病死率差异均无统计学意义(P>0.05)；PSM后，两组患者上述指标差异仍无统计学意义(P>0.05)。PSM前，两组患者PT及TT差异无统计学意义(P>0.05)，而APTT、FIB、FDP、D-二聚体及AT3水平差异有统计学意义(P<0.05)；PSM后，两组患者PT、APTT及TT差异无统计学意义(P>0.05)，FIB、FDP、D-二聚体及AT3水平差异仍有统计学意义(P<0.05)。PSM前，两组患者的R及LY30差异无统计学意义(P>0.05)，而K、Angle、MA及CI差异有统计学意义(P<0.05)；PSM后，两组患者R、LY30及CI差异无统计学意义(P>0.05)，K、Angle及MA差异仍有统计学意义(P<0.05，表1)。
2.2 随机森林筛选变量的结果
采用随机森林算法对24个变量进行分析，包括基础指标如年龄、性别、入科时ISS评分、APACHEⅡ评分，入科后2 h的白细胞、红细胞、血小板计数、血红蛋白，谷丙转氨酶、谷草转氨酶、总胆红素、肌酐及总蛋白，PT、APTT、TT、FIB、FDP、D-二聚体、AT3，R、K、Angle、MA等，结果显示，血栓弹力图MA值高是创伤后血栓事件的危险因素(P<0.05，图1)。
2.3 MA预测创伤患者发生血栓事件的ROC曲线分析
ROC曲线分析结果显示，血栓弹力图MA值预测创伤患者发生血栓事件的曲线下面积(AUC)为0.70(95%CI 0.56~0.81，P<0.01，图2)。bootstrap法验证得出的AUC为0.70(95%CI 0.57~0.80，P<0.01)。MA的临界值为63.3 mm，预测创伤患者发生血栓事件的敏感度为63.6%，特异度78.4%。根据此临界值将经倾向性评分匹配后的创伤患者重新分组，结果显示，MA≥63.3 mm时血栓事件的发生率为42.4%(14/33)，高于MA<63.3 mm时血栓事件的发生率(10.4%，8/77)，差异有统计学意义(χ2=14.816，P<0.001)。
3 讨论
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发生创伤时，组织损伤导致大量组织因子进入血液，激活外源性凝血途径；同时血管内皮细胞损伤导致内皮下胶原暴露，激活内源性凝血途径。创伤早期由于止血的需要，机体可表现为高凝状态；随着出血量增加，组织损伤、炎症、休克的发生导致凝血因子活性下降、血小板计数减少及纤溶亢进，进而形成创伤性凝血病，凝血状态整体由高凝向低凝转化[13]。当创伤性凝血病被纠正后，可出现血小板继发性增多，导致创伤恢复期高凝倾向[14]。本研究对255例创伤患者进行回顾性病例对照研究，探讨其发生血栓事件的风险因素，结果显示，PSM前，与无血栓组相比，血栓组的纤维蛋白原水平较高，APTT缩短，FDP及D-二聚体水平均降低；PSM后，血栓组的纤维蛋白原仍高于无血栓组，FDP和D-二聚体水平仍低于无血栓组；提示创伤后发生血栓事件的患者在创伤早期存在明显高凝倾向及纤溶活动偏弱的状态。
血栓弹力图针对全血标本进行检测，能够判断患者整体的凝血状态，尤其对高凝状态的判断具有优势。本研究结果显示，与无血栓组相比，血栓组的K值缩短、Angle角变大，提示纤维蛋白原功能相对增强；血栓组的MA值明显升高，提示血小板功能相对亢进。血栓弹力图结果显示血栓组整体状态具有高凝倾向，与常规凝血项目检测结果一致。采用随机森林算法筛选变量，结果显示只有MA值高是创伤后血栓形成的危险因素。ROC曲线分析显示MA判断创伤患者血栓形成的AUC为0.70，当MA界值为63.3 mm时，预测创伤患者发生血栓事件的敏感度为63.6%，特异度为78.4%，其结果与bootstrap法验证得出的AUC一致，表明MA值对创伤后是否发生血栓具有较好的预测价值。血栓弹力图中MA是血小板及纤维蛋白原共同作用决定的，其中血小板的贡献度约占80%[15]。Sumislawski等[16]研究发现，如果脑钝器伤患者行血栓弹力图检查发现MA≥63 mm，则出现脑梗死的风险较MA<63 mm的患者增加4.3倍。Meier等[17]研究发现，肾功能不全合并脑出血患者可出现以MA≥67 mm为特征的高凝状态。上述研究均表明MA值是预测血栓事件的敏感指标。
纤溶相对抑制是创伤后患者并发血栓事件的重要因素。本研究发现，血栓组的D-二聚体、FDP及血栓弹力图中的LY30低于无血栓组。国外已有研究认为LY30<0.8%属于纤溶抑制，LY30≥3%属于纤溶亢进[18]，但该标准是否适用于亚洲人群尚无相关证据。本研究显示，无血栓组LY30的第三四分位值为0.5%，提示中国人群应用血栓弹力图诊断纤溶抑制的标准可能与国外人群不同。此外，这种纤溶相对抑制也可能与抗纤溶药物的使用有关。现行指南依据循证医学证据要求，对于创伤性大出血患者，需立即静脉注射1 g氨甲环酸[19]，但过度使用氨甲环酸会增高血栓事件的发生率[20]。本研究结果提示，如行血栓弹力图检查显示创伤患者的LY30偏低，应谨慎使用抗纤溶药物。
综上所述，本研究发现血栓弹力图的MA值高是创伤患者并发血栓事件的危险因素。当创伤患者MA≥63.3 mm时，临床医师需评估患者是否已发生血栓事件，并根据检查结果采取相应的预防及治疗措施。作为单中心研究且例数偏少是本研究的不足之处，扩大病例数及个性化使用抗纤溶药物为下一步研究的方向。
基金
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  • 江西省卫健委科技计划(20204819)
文献
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2023年第48卷第1期
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doi: 10.11855/j.issn.0577-7402.2023.01.0078
  • 接收时间：2022-01-27
  • 首发时间：2025-12-03
  • 出版时间：2023-01-28
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  • 收稿日期：2022-01-27
  • 录用日期：2022-04-10
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Science and Technology Plan of Jiangxi Provincial Health Commission(20204819)
江西省卫健委科技计划(20204819)
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    解放军联勤保障部队第908医院重症医学科/南昌市血栓与止血学重点实验室，江西南昌 330002

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宋景春，E-mail：
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2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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